The purpose of the reproductive epidemiology project is to develop and apply methods for measuring damage to human reproduction. Such damage can include infertility, endocrine dysfunction, menstrual disorders, subclinical pregnancy loss, clinically recognized pregnancy loss (miscarriage), impaired fetal growth or other intrauterine damage, and perinatal death. Many of these reproductive endpoints have been poorly studied in humans. We are exploring all these endpoints as possible tools for detecting toxic effects on human health. In several instances, we are using exposure to a known toxin as a way to develop our methods for studying reproductive effects. DES is a synthetic estrogen with well-known toxic effects in animal models. Among a group of persons exposed to DES prenatally, we are looking for effects on endocrine and menstrual function, male fertility, immune function, and cognitive development. Evidence for DES effects on any of these endpoints would justify further study of those endpoints in other populations that may be exposed to reproductive toxins. Meanwhile, we continue our development of epidemiologic methods for studying early pregnancy loss and birthweight. In addition, we are exploring genetic conditions which may affect susceptibility of populations to reproductive toxins. Specifically, we are investigating a mutation of the estrogen receptor gene which has been reported to be associated with a high risk of pregnancy loss.